Clinical Drug Experience Knowledgebase

Criteria

Inclusion Criteria:

Confirmed diagnosis of Cystic Fibrosis based on the following criteria:

positive sweat chloride 60 mEq/liter (by pilocarpine iontophoresis); and/or
a genotype with two identifiable mutations consistent with CF
Presence of Pseudomonas aeruginosa, Staphylococcus aureus or Stenotrophomonas maltophilia in the screening sputum culture.
Chronic microbial lung colonization (≥6 months) with presence of Pseudomonas aeruginosa, Staphylococcus aureus or Stenotrophomonas maltophilia in at least two (2) sputum cultures in the past year (the screening culture can count as one of the two positive cultures).

Ongoing chronic inhaled antibiotic therapy for at least 3 months prior to (screening or baseline).

• For subjects on cycled therapy, at least 2 cycles of drug need to have been completed prior to baseline.

Willing to be off of inhaled antibiotic therapy from Day 1 to Day 15
Male or female subjects ≥18 years
FEV1 <85% and >35% at screening and baseline
SaO2 >90% on room air at screening and baseline
Clinically stable with no significant changes in health status within 14 days prior to Baseline
Written Informed Consent and HIPAA authorization
Non-smoker for at least 6 months prior to screening and agrees not to smoke during the study
Chest x-ray within the last six (6) months. If none, a chest x-ray is required before randomization.
Willing and able to comply with the treatment schedule and procedures.

Exclusion Criteria:

Initiation of any new chronic therapy (e.g., ibuprofen, Pulmozyme®, hypertonic saline, azithromycin, TOBI®, Cayston®) within 4 weeks prior to screening.
Use of antibiotics [oral, intravenous (iv), and/or inhaled] for acute respiratory symptoms within 2 weeks prior to baseline.
Significant hemoptysis within 30 days prior to screening (≥5 mL of blood in one coughing episode or >30 mL of blood in a 24 hour period)

History of colonization with nontuberculosis mycobacterium in sputum culture. The investigator can be guided by the following suggested criteria for a subject to be considered free of colonization:

Two respiratory tract cultures negative for NTM in the last year, with no subsequent positive cultures; and
these 2 respiratory cultures must be separated by at least 3 months; and
one of these two cultures has to have been obtained within the last 6 months
Cardiac (left heart) insufficiency (defined as LVEF <35%) at screening
Use of a nitric oxide donor agent such as nitroglycerin or drugs known to increase methemoglobin such as lidocaine, prilocaine, benzocaine or dapsone at screening

Any of the following abnormal lab values at Screening:

Hemoglobin < 10 g/dl
Methemoglobn >3%
Platelet count <100,000/mm3
Prothrombin time international ratio (INR) > 1.5
Abnormal liver function defined as any two of the following:
ALT >3 x ULN
AST >3 x ULN
ALP > 3 x ULN
GGT > 3 x ULN
Abnormal liver function defined as:
ALT >5 x ULN
AST >5 x ULN
Abnormal renal function defined as:
Calculated Creatinine Clearance < 50 mL (as calculated by Cockcroft/Gault)

For women of child bearing potential:

positive pregnancy test at screening or
lactating or
unwilling to practice a medically acceptable form of contraception from screening to Day 36 (acceptable forms of contraception: abstinence, hormonal birth control, intrauterine device, or barrier method plus a spermicidal agent)
Use of an investigational drug within 30 days prior to screening
Intravenous or oral steroids in the 14 days prior to screening
Current use of inhaled steroids >500 micrograms twice daily of Fluticasone or equivalent in the 30 days prior to screening
Use of supplemental oxygen (daytime or nocturnal) in the 7 days prior to screening
Any condition that the Investigator believes would interfere with the intent of this study or would make participation not in the best interest of the subject